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Shifts in targeting of class switch recombination sites in mice that lack mu switch region tandem repeats or Msh2.

ABSTRACT: The mechanisms that target class switch recombination (CSR) to antibody gene switch (S) regions are unknown. Analyses of switch site locations in wild-type mice and in mice that lack the Smu tandem repeats show shifts indicating that a 4-5-kb DNA domain (bounded upstream by the Imu promoter) is accessible for switching independent of Smu sequences. This CSR-accessible domain is reminiscent of the promoter-defined domains that target somatic hypermutation. Within the 4-5-kb CSR domain, the targeting of S site locations also depends on the Msh2 mismatch repair protein because Msh2-deficient mice show an increased focus of sites to the Smu tandem repeat region. We propose that Msh2 affects S site location because sequences with few activation-induced cytidine deaminase targets generate mostly switch DNA cleavages that require Msh2-directed processing to allow CSR joining.

SUBMITTER: Min IM

PROVIDER: S-EPMC2212040 | biostudies-literature | 2005 Jun

REPOSITORIES: biostudies-literature

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Shifts in targeting of class switch recombination sites in mice that lack mu switch region tandem repeats or Msh2.

Min Irene M IM Rothlein Lisa R LR Schrader Carol E CE Stavnezer Janet J Selsing Erik E

The Journal of experimental medicine 20050613 12

The mechanisms that target class switch recombination (CSR) to antibody gene switch (S) regions are unknown. Analyses of switch site locations in wild-type mice and in mice that lack the Smu tandem repeats show shifts indicating that a 4-5-kb DNA domain (bounded upstream by the Imu promoter) is accessible for switching independent of Smu sequences. This CSR-accessible domain is reminiscent of the promoter-defined domains that target somatic hypermutation. Within the 4-5-kb CSR domain, the target ...[more]

PMID: 15955838

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